RT Journal Article SR Electronic T1 DCAF4, a novel gene associated with leucocyte telomere length JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 157 OP 162 DO 10.1136/jmedgenet-2014-102681 VO 52 IS 3 A1 Massimo Mangino A1 Lene Christiansen A1 Rivka Stone A1 Steven C Hunt A1 Kent Horvath A1 Dan T A Eisenberg A1 Masayuki Kimura A1 Inge Petersen A1 Jeremy D Kark A1 Utz Herbig A1 Alex P Reiner A1 Athanase Benetos A1 Veryan Codd A1 Dale R Nyholt A1 Ronit Sinnreich A1 Kaare Christensen A1 Hisham Nassar A1 Shih-Jen Hwang A1 Daniel Levy A1 Veronique Bataille A1 Annette L Fitzpatrick A1 Wei Chen A1 Gerald S Berenson A1 Nilesh J Samani A1 Nicholas G Martin A1 Sarah Tishkoff A1 Nicholas J Schork A1 Kirsten Ohm Kyvik A1 Christine Dalgård A1 Timothy D Spector A1 Abraham Aviv YR 2015 UL http://jmg.bmj.com/content/52/3/157.abstract AB Background Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).Results Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10−10) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10−3 and 2×10−3, respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10−169 to 3.42×10−24.Conclusions We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.